Irradiance (Rate) Dependencies on the Microvascular Response of Photodynamic Therapy as Monitored by Interstitial Doppler Optica

Photodynamic therapy (PDT) is novel treatment option for recurrent prostate cancer. Although this technique appears to be promising, several challenges remain in quantifying the tissue response to treatment, such as vascular response. Monitoring and quantifying this biological response in real-time may provide early assessment of treatment efficacy. An exciting and unique approach to image and quantify the PDT-induced vascular response is Doppler optical coherence tomography (DOCT). DOCT exhibits micron-scale spatial resolution allowing visualization of structures at near-cellular-levels, and yields flow velocity resolution of ~100 µm/s (in vivo). Needle based IS-DOCT is an attractive approach for deep in vivo tissue assessment. An interstitial (IS) needle probe (22 gauge, OD=0.7mm) was developed for minimally invasive monitoring of the microvascular response to PDT deep within tumor tissue. Rats were administered a light sensitizing drug, Photofrin, and 20-24 h later the tumours were irradiated superficially at 635nm with irradiance rates of 13-180 mW/cm2 for 25 minutes, to total light doses of 25-200 J/cm2. Results demonstrate different rates of vascular shutdown within the tumor, depending on PDT irradiance rate and light dose. Controls (needle + light, needle only) showed no significant microvascular changes. Three dimensional high frequency ultrasound imaging was also performed to confirm IS-DOCT needle placement and image gross tissue architecture. Microvascular shutdown occurred at different rates and correlated with PDT light dose and irradiance rate. These dependencies may play an important role in pre-treatment planning, feedback control for treatment optimization, and post PDT treatment assessment. Although this study’s primary goal was improving the ability to monitor and quantify PDT in prostate cancer, the techniques developed here can be applied to PDT of other solid organs, and for real-time monitoring of other vascularly targeted cancer treatments (i.e. anti-angiogenic chemotherapy)

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